Rh blood group phenotyping is required both before blood transfusion and also to determine if potential Rh incompatibility exists in pregnant women. Normally the Rh phenotype is established by a hemagglutination test. However, a limiting factor with available reagents is that human IgG anti-Rh is unable to induce direct red cell agglutination. Although 1gM monoclonal antibodies can directly agglutinate Rh positive red blood cells, anti-Rh IgMs are frequently polyreactive and give false positives. We propose to develop a novel human blood typing reagent consisting of a human 1gM-like (polymeric) recombinant antibody containing the constant regions of human IgG and the variable regions of human anti-Rh monoclonal antibodies. We hypothesize that this anti-Rh polymeric IgG will be able to directly agglutinate Rh positive red blood cells making Rh phenotyping easier, more accurate and less expensive. We also hypothesize that this anti-Rh polymeric IgG will be a novel therapeutic in humans for prophylaxis of the hemolytic disease of the newborn due to Rh incompatibility (Rh-HDN) and for the treatment of idiopathic or HIV-related thrombocytopenic purpura. Using our approach it is possible both to use variable regions of differing specificity and affinity and constant regions with different associated effector functions. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE